Endocrine System II (b) Flashcards
Celluar Components of the Adeno-Hypophysis (Anterior pituitary)
basophilic, eosinophilic and
chromophobic cytoplasm
Anterior Pituitary (Adeno-Hypophysis) produces?
PRL, GH,
ACTH, FSH, LH and TSH
Celluar Components of the Posterior Pituitary (Neuro-Hypophysis)
modified glial cells (pituicytes) and axonal
processes from Hypothalamus
Posterior Pituitary (Neuro-Hypophysis) produces?
Oxytocin and ADH (or Vasopressin)
loc of the pituitary gland
Base of the brain, within Sella turcica
(bellow the hypotahlamus connected by a stalk-composed of axons)
Cause of Hyperpituitarism
*Excessive secretion of trophic hormones
Anterior Pituitary Aden.
Cause of Hypopituitarism
* Deficiency of trophic hormones
Ischaemic injury, surgery, radiation, inflammatory reactions, Non-functional Pituitary Adenomas (through compression of adjacent normal tissue)
Complictions of Pituitary Adenoma
i. Visual field defects (bitemporal hemianopsia),
ii. Elevated intra-cranial pressure (headache, nausea, vomiting),
iii. Seizures or obstructive hydrocephalus
iv. Pituitary apoplexy (acute haemorrhage in an Adenoma)
Causes of Hyperpituitarism
& Pituitary Adenomas
- Anterior Pituitary Adenoma (most common)
- Hyperplasia
- Pituitary Carcinoma
- Secretion of hormones by extra-pituitary tumour
patho of Hyperpituitarism
& Pituitary Adenomas
*GNASI gene mutations (a-subunit of Gs protein)
–> Persistent generation of cAMP –> Unchecked cellular proliferation;
About 40% of GH-secreting Somatotroph Cell Adenomas
Genes involved in the development of familial Pituitary Adenomas (Prolactinoma)?
MEN 1, CDKNIB, PRKARIA
and AIP
* Familial Pituitary Adenomas
Mutations of ——– gene are associated with an
aggressive behaviour , such as invasion and
recurrence
TP53
Microscopic Findings:
* Uniform, polygonal cells arranged in sheets, cords or papillae
* Uniform or pleomorphic nuclei (Monomorphic
appearance of tumour cells)
* Low mitotic index
* Acidophilic, basophilic or chromophobic cytoplasm
* Sparse supporting connective tissue or reticulin
* Small round cells
* Small round nuclei
* Pink to blue cytoplasm
PITUITARY ADENOMAS (Anterior)
Epi of Prolactinomas
Most common type of functional
Pituitary Adenomas
CF of Prolactinomas
- Hyperprolactinaemia
- Amenorrhoea
- Galactorrhoea
- Loss of libido
- Infertility
What is Pituitary Stalk effect ?
Hyperprolactinaemia caused by a mass
(other than Prolactinoma) in the supra-sellar
compartment –> which inhibits the normal inhibitory influence of Hypothalamus on Prolactin secretion
Microscopic features:
* Chromophobic cells (clear cells)
* Sphaerical microcalcifications
Prolactinomas
Epi of Growth Hormone-Producing
(Somatotroph) Adenomas
Second most common type of
functional Pituitary Adenomas
Microscopic features:
* Densely or sparsely granulated cells
* Paranuclear “fibrous body”
Growth Hormone-Producing (Somatotroph) Adenomas
*Paranuclear bodies = indication of Pituitary adenomas
* GH-Producing (Somatotroph) Adenomas
Overproduction and release of GH leads to hepatic
secretion of —— –>
–> In cases of prepubertal children (before closure of epiphyses) —-> —————–
–> After closure of epiphyses –> ————–
secretion of IGF-1
Before –> Giganitism
After (adults) –> Acromegaly
CF of Growth Hormone-Producing
(Somatotroph) Adenomas
- Gigantism or Acromegaly
- Abnormal Glucose tolerance
- Diabetes Mellitus
- Generalised muscle weakness
- Hypertension
- Arthritis
- Osteoporosis
- Congestive Heart Failure
Epi of ACTH-Producing Adenomas
- Commonly, Micro-Adenomas
- Clinically silent or manifested as Cushing Syndrome
Cause of Nelson Syndrome
Development of large (Macro-adenomas), aggressive ACTH Adenomas, after removal of both Adrenal Glands,
for treatment of Cushing Syndrome
Absence of Adrenal Glands –> {No/yes} Hypercortisolism
No
CF of Nelson Syndrome
i. Hyperpigmentation of the skin,
ii. Headaches and
iii. Vision impairment
Lab findings of Nelson Syndrome
↑ levels of ACTH and
β-MSH
CF of Gonadotroph (FSH- and LH-producing) Adenomas
- Impaired vision,
- headaches,
- diplopia (double vision),
- pituitary apoplexy
Immunohistochemistry of Gonadotroph (FSH- and LH-producing) Adenomas
+ve for : common Gonadotropin α-subunit , the specific β-FSH and β-LH subunits
Epi of Thyrotroph (TSH-producing) Adenomas
- 1% of Anterior Pituitary Adenomas
- Rare cause of Hyperthyroidism
Epi of Non-functional Pituitary Adenomas
25% of all pituitary tumours (posterior)
CF of Non-functional Pituitary Adenomas
- Typical presentation of mass effects
- Compromise of the residual Anterior
Pituitary –> Hypopituitarism
Epi of Pituitary Carcinomas
Rare occurrence
Microscopic features:
Rosettes of small cells
Monomorphic (pleomorphic) chromatin-rich nuclei
Null-Cell Adenomas (aka Hormone-negative adenomas)
*Null-cell adenomas have abscense of immuno-histochemical reactivity
———— : Hypofunction of the Anterior Pituitary, after loss or absence of >75% of the Anterior Pituitary
parenchyma
Hypopituitarism
Causes of Hypopituitarism
1) Hypopituitarism, accompanied by Diabetes
Insipidus, is almost always of hypothalamic
origin
2) Non-functioning Pituitary Adenomas
3) Ablation of the Pituitary Gland by surgery or irradiation
4) Inflammatory disorders (e.g. Sarcoidosis, Tbc),
5) trauma and metastatic neoplasms
6) Sheehan’s syndroms or postpartum necrosis of Anterior Pituitary Gland
7) Other causes of ischaemic necrosis: DIC, sickle cell anaemia, trauma, shock, etc.
CF of Hypopituitarism (depending on hormone(s) lacking)
- GH-deficiency –> —–
- GnRH deficiency –> ——- (F); —— (M)
- PRL deficiency –> ———-
- TSH deficiency –> ——–
- ACTH deficiency –> ———
- GH-deficiency –> Dwarfism (in children)
-
GnRH deficiency–> Amenorrhoea and Infertility
(F); Decreased Libido and Impotence (M) - PRL deficiency –> Failure of postpartum Lactation
- TSH deficiency –> Hypo-Thyroidism
- ACTH deficiency –> Hypo-Adrenalism
*GnRH: Gonadotropin-Releasing Hormone
causes of Empty sella Turcica
- Pituitary compression through herniation of the Arachnoidea (Arachnoid mater)
- Sheehan syndrome
- Total infarction of an Adenoma
- Operation or Radiation of the Hypophysis
Posterior Pituitary Syndromes examples
1) Central Diabetes Insipidus
2) Syndrome of Inappropriate ADH (SIADH) secretion
* Posterior Pituitary Syndromes
Causes of Syndrome of Inappropriate ADH (SIADH) secretion
- Ectopic ADH secretion, by a malignant neoplasm
(e.g. SCLC) - Non-neoplastic diseases of the lung
- Local injury to the Hypothalamus or Neuro-Hypophysis
* Posterior Pituitary Syndromes
patho of Syndrome of Inappropriate ADH (SIADH) secretion
Resorption (loss) of excessive amounts of free water –> Hyponatraemia (low Na+)
* Posterior Pituitary Syndromes
CF of Syndrome of Inappropriate ADH (SIADH) secretion
- Cerebral oedema –> Neurologic dysfunction
- Normal blood volume and NO peripheral oedema
* Posterior Pituitary Syndromes
Cause of Central Diabetes Insipidus
- Idiopathic
- Head trauma
- Neoplasms
- Inflammatory disorders
* Posterior Pituitary Syndromes
Lab findings of Central Diabetes Insipidus
Increased serum Sodium and osmolality, as a result of excessive renal loss of free H2O
* Posterior Pituitary Syndromes
Cf of Central Diabetes Insipidus
- Polyuria (dilute urine, with low specific gravity)
- Polydipsia
MoI of MEN-1 + mutation
MoI: AD
Mutation: inactivation of both alleles of the MEN-1 gene
MEN-1 loc+ examples
- 1) parathyroid –> Primary Hyperparathyroidism, due to Hyperplasia or Adenoma; Most common
manifestation in MEN-1 (80-95% of cases)
2) Pituitary –> Prolactinoma (Prolactin-secreting Macroadenoma)
3) Pancrease –> *insulinomas** (zollinger Elison syndrome)
MEN-2 moI+MUTATION
MoI: AD
Mutation: germ-line RET mutations, activating mutations of the RET proto-oncogene
MEN-2
All persons with germ-line RET mutations should
undergo prophylactic thyroidectomy to prevent the unavoidable development of ?
Medullary
Carcinomas
Loc of MEN-2A +examples
1) Thyroid: Medullary Carcinomas
2) Adrenal Medulla –> Pheochromocytomas;
3) Parathyroid: 10-20% of patients –>
Development of Parathyroid Gland Hyperplasia
–> Primary Hyperparathyroidism
Endocrine Manifestations in MEN-1
- Zollinger-Ellison Syndrome associated with
Gastrinomas - Hypoglycaemia associated with Insulinomas
MEN-2B involves?
Thyroid (Medullary carcinoma) and the Adrenal Medulla (pheochromocytoma)
Thyroid and Adrenal Medulla disease shows
similarities to MEN-2A, with the following
differences:
* MEN-2B patients do not develop Primary
Hyperparathyroidism
* Extra-endocrine manifestations in MEN-2B
patients:
* Ganglio-Neuromas of mucosal sites
(GI tract, lips, tongue)
* Marfanoid habitus
